The goal of the Organophosphorus Nerve Agent Testing (ONAT) Core, a component of the Center for[unreadable] Catalytic Bioscavenger Medical Defense Research, is to test the mutant enzymes produced by other[unreadable] Research Projects in the Center for in vitro and in vivo efficacy against organophosphorus (OP) nerve[unreadable] agents. The results from this testing will contribute directly to the development of a pretreatment that offers[unreadable] complete protection from poisoning by OPs. The core is located at the US Army Medical Research Institute[unreadable] of Chemical Defense, a singular national resource with a highly trained staff of scientists supported by[unreadable] safety, surety, and environmental specialists who ensure regulatory compliance of experiments involving[unreadable] highly toxic surety agents such as OP nerve agents. The mission of the USAMRICD is the development of[unreadable] medical countermeasures against chemical weapons, which is precisely aligned with the mission of the[unreadable] CounterACT initiative. The ONAT core is uniquely positioned to assess the function of anti-OP[unreadable] bioscavengers against bona fide nerve agents; the use of these highly toxic agents is restricted to a very[unreadable] limited number of research facilities worldwide. The tests to be conducted by the core will include[unreadable] characterization of the OP nerve agent reactivity, specificity, and stereoselectivity of candidate bioscavenger[unreadable] enzymes using a combination of colorimetric, calorimetric, and gas chromatographic/mass spectroscopy[unreadable] approaches. The capacity of different enzymes to persist in the circulation of a model test animal, and the[unreadable] protection from OP toxicity afforded by these enzymes will also be evaluated. The multidisciplinary approach[unreadable] of the ONAT core to assay development and efficacy testing will support the development of a 'next[unreadable] generation' bioscavenger molecule with the potential to bind and destroy OP nerve agents in the blood,[unreadable] before they distribute to the brain, central nervous system, and other toxic targets. In this regard it is[unreadable] important that the USAMRICD, and in particular the PI of the Center as well as the PI for this core[unreadable] component, have experience in both basic science and in early product development, meaning attention will[unreadable] constantly remain focused on not only the scientific issues, but also on the requirements to develop a novel,[unreadable] protein based drug product that will protect against the otherwise toxic effects of OP nerve agent exposure.[unreadable] The goal of the CounterACT program is to create new ways to protect ourselves from toxic chemicals like[unreadable] OP nerve agents. The goal of this core proposal is to test how well these new approaches defend against[unreadable] highly toxic nerve agents. Without the testing that will be conducted by this core, which is unique in its[unreadable] access to OP nerve agents, there will be no way to measure the effectiveness of these new approaches.